The invention relates broadly to ophthalmic technology. More specifically, this invention relates to the therapeutic treatment of the eye to reduce elevated intraocular pressure, for example, the elevated intraocular pressure which is associated with glaucoma.
U.S. Pat. No. 5,208,256 teaches a method of treating ocular hyertension by ocularly administering a combination of a docosanoid compound, e.g., [1R-[1xcex1(Z),2xcex2,3xcex1,5xcex1]]-7-[3,5-Dihydroxy-2-(3-oxodecyl)cyclopentenyl]-5-heptenoic acid or a salt or ester thereof and a polyoxyethylenesorbitan unsaturated higher aliphatic acid monoester. Preferred examples of the latter includes myristoleic acid, palmitoleic acid, oleic acid, gadoleic acid and linoleic acid. Polyoxyethylene (20) sorbitan monooleate is also known as Polysorbate 80 and sold, inter alia, under the names SORLATE, CRILLET, TWEEN 80, MONITAN and OLOTHORB.
CREMOPHOR has been used as a surfactant in eye drops (See Japanese Patent 07316060, filed on Dec. 16, 1994). CREMOPHOR is an ethoxylated, hydrogenated castor oil, which is also referred to as a polyoxyethylene hardened castor oil. However, the use of CREMOPHOR with docosanoids in an ophthamic delivery system has not been disclosed or suggested.
While docosanoids are useful for reducing intraocular pressure, there is a need to improve the efficacy of medicaments containing them. In addition, there is a need for improvement in the preservative effectiveness of ophthalmic docosanoid compositions which include surfactants, while maintaining good efficacy and good ocular tolerance. Furthermore, improvements in the shelf life of ophthalmic docosanoid compositions are desirable. Also, it is always desirable to reduce manufacturing difficulties. Thus, there is a need for a docosanoid-containing ophthalmic composition that can be manufactured with a minimum of complexity and which exhibits a balance of efficacy, preservative effectiveness, ocular tolerance, and a long shelf life.
An object of the invention is to improve the efficacy of docosanoid-containing ophthalmic compositions.
Another object of the invention is to improve the preservative effectiveness of docosanoid-containing ophthalmic compositions.
Still another object of the invention is to improve shelf life of docosanoid-containing ophthalmic compositions.
Yet another object of the invention is to reduce the complexity of manufacturing a docosanoid-containing ophthalmic composition.
A further object of the invention is to produce a docosanoid-containing ophthalmic composition with a desirable balance of efficacy, preservative effectiveness, ocular tolerance, and shelf life.
These and other objects and advantages of the invention are achieved with the various embodiments of the present docosanoid-containing ophthalmic compositions, methods of use and methods of manufacture. One embodiment of the invention is an ophthalmic composition which includes a docosanoid, a non-ionic surfactant (e.g. a CREMOPHOR) and a preservative (e.g. benzalkonium chloride). Another embodiment is an ophthalmic composition which includes a docosanoid, a surfactant, a non-ionic tonicity adjusting agent (e.g. mannitol) and a preservative. Still another embodiment is an ophthalmic composition which includes a docosanoid, one or more surfactants, a strong preservative (e.g. BAK) and a preservative enhancer (e.g., EDTA). Yet another embodiment of the invention relates to adding a buffer to improve product shelf life and reduce production complexity.